Zhang Feng, Jiang Ruiya, Sun Shishi, Wu Caiyun, Yu Qimeng, Awadasseid Annoor, Wang Jianwei, Zhang Wen
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou, 310014, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou, 310014, China; Moganshan Institute, Zhejiang University of Technology, Deqing, China.
Eur J Med Chem. 2024 Mar 15;268:116267. doi: 10.1016/j.ejmech.2024.116267. Epub 2024 Feb 23.
PD-L1 is an important immune checkpoint protein that can bind to T cells' PD-1 receptor, thereby promoting immune escape from tumors. In recent years, many researchers have developed strategies to degrade PD-L1 to improve the effect of immunotherapy. The study of degrading PD-L1 provides new opportunities for immunotherapy. Here, we mainly summarize and review the current active molecules and mechanisms that mediate the degradation of immature and mature PD-L1 during the post-translational modification stages, involving PD-L1 phosphorylation, glycosylation, palmitoylation, ubiquitination, and the autophagy-lysosomal process. This review expects that by degrading PD-L1 protein, we will not only gain a better understanding of oncogenic mechanisms involving tumor PD-L1 protein but also provide a new way to improve immunotherapy.
程序性死亡配体1(PD-L1)是一种重要的免疫检查点蛋白,它可以与T细胞的程序性死亡受体1(PD-1)结合,从而促进肿瘤的免疫逃逸。近年来,许多研究人员开发了降解PD-L1的策略,以提高免疫治疗的效果。对PD-L1降解的研究为免疫治疗提供了新的机遇。在此,我们主要总结和综述目前在翻译后修饰阶段介导未成熟和成熟PD-L1降解的活性分子和机制,包括PD-L1的磷酸化、糖基化、棕榈酰化、泛素化以及自噬-溶酶体过程。本综述期望通过降解PD-L1蛋白,我们不仅能更好地理解涉及肿瘤PD-L1蛋白的致癌机制,还能为改善免疫治疗提供新途径。